Sodium Hydroxide → (2R,3S)-3-(3,4-dimethoxyphenylsulfanyl)-2-methyl-7-phenylheptanoic acid

Participants

Reaction Steps

A solution of 3,4-dimethoxybenzenethiol (0.35 g, 2.1 mmol) in isopropanol (2 mL) is cooled in an ice bath and 1 M sodium hydroxide (1.5 mL, 1.5 mmol) is added slowly. This mixture is then added to a 0° C. solution of (3S,4R)-3-methyl-4-(4-phenylbutyl)oxetan-2-one (0.30 g, 1.4 mmol) in isopropanol (2 mL) over 3 minutes. The reaction is stirred for 5 minutes in ice and then allowed to warm to room temperature. After stirring for a total of 1.5 hours, the reaction is neutralized with HCl/ether. Methanol is added and the reaction mixture is azeotroped twice. The crude product is purified by gradient elution column chromatography (silica, 1 to 5% MeOH in CH2Cl2) to yield (2R,3S)-3-(3,4-dimethoxyphenylsulfanyl)-2-methyl-7-phenylheptanoic acid (0.48 g, 90%): 1H NMR (300 MHz, CDCl3) δ 7.29-7.25 (m, 2H), 7.19-7.14 (m, 3H), 7.03-6.99 (m, 2H), 6.79 (d, J=8.2 Hz, 1H), 3.86 (s, 3H), 3.85 (s, 3H), 3.35-3.25 (m, 1H), 2.71-2.61 (m, 1H), 2.60 (t, J=7.0 Hz, 2H), 1.75-1.37 (m, 6H), 1.23 (d, J=7.0 Hz, 3H); MS (ion spray) m/e 389 (M+).

Provenance & Evidence